Is SRCAP p.Ile106Val (c.316A>G) pathogenic?

SRCAP p.Ile106Val (c.316A>G) is classified Uncertain significance in SRCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-13). AlphaMissense: ambiguous (0.4826); Very rare (popmax 0.00534%, afr); Associated with Floating-Harbor syndrome.

What condition is associated with SRCAP p.Ile106Val (c.316A>G)?

SRCAP p.Ile106Val (c.316A>G) is associated with Floating-Harbor syndrome (ClinVar).

How common is SRCAP p.Ile106Val (c.316A>G) in the general population?

SRCAP p.Ile106Val (c.316A>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about SRCAP p.Ile106Val (c.316A>G)?

AlphaMissense predicts ambiguous (score 0.4826) — an in-silico prediction, not a clinical call.

SRCAP p.Ile106Val

c.316A>G · rs777066101 · VCV1033132

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Floating-Harbor syndrome

Computational evidence

Protein change
AlphaMissense	0.4826	ambiguous
REVEL	0.218	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 5,369 bp · p 5.9e-15 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,924 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000496% 8/1,614,032 alleles · very rare exomes 4/1,461,858 · genomes 4/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,731
European (non-Finnish)	0.000339%	295,008

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: SRCAP
Protein: p.Ile106Val
Coding: c.316A>G
MANE Select: NM_006662
dbSNP: rs777066101
Type: single nucleotide variant
Location: chr16:30707192 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 106: an α-helix

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

Disease context

Floating-Harbor syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRCAP p.Ile106= Likely benign ★ same residue
SRCAP p.Arg2329Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2435Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2444Ter Pathogenic ★★ same condition
SRCAP p.Arg2718Ter Pathogenic/Likely pathogenic ★★ same condition
SRCAP p.Arg2748Ter Pathogenic ★★ same condition
SRCAP p.Gln2407Ter Pathogenic ★★ same condition
SRCAP p.Gln2419Ter Pathogenic ★★ 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/srcap-p-ile106val (accessed [today's date]).

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