Is SON p.Thr511Lys (c.1532C>A) pathogenic?

SON p.Thr511Lys (c.1532C>A) is classified Likely benign in SON (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: ambiguous (0.3765); Ultra-rare (popmax 0.0156%, eas); Associated with Inborn genetic diseases.

What condition is associated with SON p.Thr511Lys (c.1532C>A)?

SON p.Thr511Lys (c.1532C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SON p.Thr511Lys (c.1532C>A) in the general population?

SON p.Thr511Lys (c.1532C>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about SON p.Thr511Lys (c.1532C>A)?

AlphaMissense predicts ambiguous (score 0.3765) — an in-silico prediction, not a clinical call.

SON p.Thr511Lys

c.1532C>A · rs375386570 · VCV2245830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3765 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3765	ambiguous
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.3, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 7,951 bp · p 0.32 · regional, not allelic
Overall
CADD	22.8	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 0.0156% East Asian · 7/44,878 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00142% 23/1,614,170 alleles · ultra-rare exomes 20/1,461,888 · genomes 3/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,411
South Asian	0.0132%	7,590
Remaining individualsnot grpmax-eligible	0.0064%	15,627

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.Thr511Lys
Coding: c.1532C>A
MANE Select: NM_138927
dbSNP: rs375386570
Type: single nucleotide variant
Location: chr21:33550763 (GRCh38)
Gene constraint: LOEUF 0.051 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.48 · 4 PDB

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-thr511lys (accessed [today's date]).

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