Is PRMT7 p.Val167Met (c.499G>A) pathogenic?

PRMT7 p.Val167Met (c.499G>A) is classified Conflicting classifications of pathogenicity in PRMT7 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-03-06). AlphaMissense: likely benign (0.1615); Rare (popmax 0.249%, mid); Associated with short stature-brachydactyly-obesity-global developmental delay syndrome.

What condition is associated with PRMT7 p.Val167Met (c.499G>A)?

PRMT7 p.Val167Met (c.499G>A) is associated with short stature-brachydactyly-obesity-global developmental delay syndrome (ClinVar).

How common is PRMT7 p.Val167Met (c.499G>A) in the general population?

PRMT7 p.Val167Met (c.499G>A) is rare (popmax 0.249%, mid) (gnomAD).

What do computational predictors say about PRMT7 p.Val167Met (c.499G>A)?

AlphaMissense predicts likely benign (score 0.1615) — an in-silico prediction, not a clinical call.

PRMT7 p.Val167Met

c.499G>A · rs138763605 · VCV1028135

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1615 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.249%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

short stature-brachydactyly-obesity-global developmental delay syndrome

Computational evidence

Protein change
AlphaMissense	0.1615	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.71, phastCons 0.55
Regional constraint	o/e 0.95	unconstrained · MANE · 41 kb · p 0.12 · regional, not allelic
Overall
CADD	17.98	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.249% Middle Eastern · 15/6,022 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0105% 168/1,603,778 alleles · rare exomes 154/1,451,498 · genomes 14/152,280 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.249%	401
South Asian	0.021%	4,763
Remaining individualsnot grpmax-eligible	0.0145%	6,894
European (non-Finnish)	0.00998%	10,023
Admixed American	0.00508%	19,683
African / African-American	0.00402%	24,889
East Asian	0.00224%	44,620
Finnishnot grpmax-eligible	0.00156%	63,914

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRMT7
Protein: p.Val167Met
Coding: c.499G>A
MANE Select: NM_019023
dbSNP: rs138763605
Type: single nucleotide variant
Location: chr16:68337566 (GRCh38)
Gene constraint: LOEUF 1.01 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.19
Residue 167: the sam-dependent mtase prmt-type 1 domain

Full PRMT7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature-brachydactyly-obesity-global developmental delay syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRMT7 c.1056-1G>T Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg274Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Arg390Ter Pathogenic ★★ same condition
PRMT7 p.Cys571Ter Pathogenic ★★ same condition
PRMT7 p.Gln323Ter Pathogenic ★★ same condition
PRMT7 p.Glu108Ter Pathogenic/Likely pathogenic ★★ same condition
PRMT7 p.Tyr159Ter Pathogenic ★★ same condition
PRMT7 p.Arg360Cys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prmt7-p-val167met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown