Is MPHOSPH6 p.Ala97= (c.291A>G) pathogenic?

MPHOSPH6 p.Ala97= (c.291A>G) is classified Benign in MPHOSPH6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-03-29). Common (popmax 9.81%, afr) — too common for a highly-penetrant pathogenic allele.

MPHOSPH6 p.Ala97=

Q: How common is MPHOSPH6 p.Ala97= (c.291A>G) in the general population?

MPHOSPH6 p.Ala97= (c.291A>G) is common (popmax 9.81%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.291A>G · rs16956538 · VCV777047

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 9.81%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -2
Overall
CADD	5.848	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.81% African / African-American · 7,359/75,044 alleles

Filtering AF 9.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.54%

Overall 0.527% 8,499/1,612,908 alleles · common exomes 4,202/1,460,558 · genomes 4,297/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	9.81%	10
Middle Eastern	0.874%	114
Remaining individualsnot grpmax-eligible	0.723%	138
Admixed American	0.596%	168
South Asian	0.0252%	3,960
European (non-Finnish)	0.0215%	4,646

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: MPHOSPH6
Protein: p.Ala97=
Coding: c.291A>G
MANE Select: NM_005792
dbSNP: rs16956538
Type: single nucleotide variant
Location: chr16:82149368 (GRCh38)
Gene constraint: LOEUF 1.6 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.57 · 3 PDB

Full MPHOSPH6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPHOSPH6 p.Glu53Gln Uncertain significance ★★ ⚠ same type
MPHOSPH6 p.Asp134Gly Benign ★★ same type
MPHOSPH6 p.Ala136Thr Uncertain significance ★ ⚠ same type
MPHOSPH6 p.Ala151Thr Uncertain significance ★ ⚠ same type
MPHOSPH6 p.Ala151Val Uncertain significance ★ ⚠ same type
MPHOSPH6 p.Asn143Ser Uncertain significance ★ ⚠ same type
MPHOSPH6 p.Asp108Val Uncertain significance ★ ⚠ same type
MPHOSPH6 p.Asp141Ala Uncertain significance ★ ⚠ same type

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/mphosph6-p-ala97 (accessed [today's date]).

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