Is SON p.Met871Val (c.2611A>G) pathogenic?

SON p.Met871Val (c.2611A>G) is classified Likely benign in SON (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-17). AlphaMissense: likely benign (0.2225); Ultra-rare (popmax 0.0921%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SON p.Met871Val (c.2611A>G)?

SON p.Met871Val (c.2611A>G) is associated with Inborn genetic diseases (ClinVar).

How common is SON p.Met871Val (c.2611A>G) in the general population?

SON p.Met871Val (c.2611A>G) is ultra-rare (popmax 0.0921%, nfe) (gnomAD).

What do computational predictors say about SON p.Met871Val (c.2611A>G)?

AlphaMissense predicts likely benign (score 0.2225) — an in-silico prediction, not a clinical call.

SON p.Met871Val

c.2611A>G · rs147398927 · VCV2048573

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0921%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2225	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 4.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 968 bp · p 9.6e-05 · regional, not allelic
Overall
CADD	22.5	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 0.0921% European (non-Finnish) · 1,087/1,179,998 alleles

Filtering AF 0.0875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0857%

Overall 0.0758% 1,224/1,613,892 alleles · ultra-rare exomes 1,132/1,461,662 · genomes 92/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0921%	1,086
Admixed American	0.0883%	1,133
Remaining individualsnot grpmax-eligible	0.088%	1,136
East Asian	0.029%	3,452
African / African-American	0.0147%	6,817
South Asian	0.00549%	18,213

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: SON
Protein: p.Met871Val
Coding: c.2611A>G
MANE Select: NM_138927
dbSNP: rs147398927
Type: single nucleotide variant
Location: chr21:33551842 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB
Residue 871: the '17 x 10 aa tandem repeats of l-a-[st]-[nsg]-[ts]-mdsqm' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SON p.Arg1112Ter Pathogenic ★★ same condition
SON p.Arg1031Cys Uncertain significance ★★ ⚠ same condition
SON p.Arg1993Cys Uncertain significance ★★ ⚠ same condition
SON p.Gly47Asp Uncertain significance ★★ ⚠ same condition
SON p.Ser1437Cys Uncertain significance ★★ ⚠ same condition
SON p.Thr1156Lys Uncertain significance ★★ ⚠ same condition
SON p.Ala1109Val Likely benign ★★ same condition
SON p.Ala1309Gly Likely benign ★★ 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/son-p-met871val (accessed [today's date]).

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