Is ITGA8 p.Ser577Phe (c.1730C>T) pathogenic?

ITGA8 p.Ser577Phe (c.1730C>T) is classified Benign in ITGA8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.1218); Common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ITGA8 p.Ser577Phe (c.1730C>T)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

ITGA8 p.Ser577Phe

Q: How common is ITGA8 p.Ser577Phe (c.1730C>T) in the general population?

ITGA8 p.Ser577Phe (c.1730C>T) is common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1730C>T · rs2298033 · VCV1238988

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 9.16%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -8.18	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 5.2	GERP 0.94, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 203 kb · p 0.032 · regional, not allelic
Overall
CADD	18.59	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 9.16% East Asian · 4,110/44,860 alleles

Filtering AF 8.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.83%

Overall 2.22% 35,776/1,613,792 alleles · common exomes 31,491/1,461,554 · genomes 4,285/152,238 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	9.58%	10
East Asiangrpmax	9.16%	11
Admixed American	4.66%	21
African / African-American	2.58%	39
Remaining individualsnot grpmax-eligible	2.21%	45
Amishnot grpmax-eligible	1.64%	61
European (non-Finnish)	1.56%	64
Ashkenazi Jewishnot grpmax-eligible	0.899%	111
South Asian	0.763%	131
Middle Eastern	0.644%	155

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ITGA8
Protein: p.Ser577Phe
Coding: c.1730C>T
MANE Select: NM_003638
dbSNP: rs2298033
Type: single nucleotide variant
Location: chr10:15607711 (GRCh38)
Gene constraint: LOEUF 0.801 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.08
Residue 577: a UniProt-annotated variant site (in)

Full ITGA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITGA8 c.2982+2T>C Pathogenic/Likely pathogenic ★★ same type
ITGA8 p.Arg938Ter Pathogenic ★★ same type
ITGA8 p.Gln876Ter Likely pathogenic ★★ same type
ITGA8 p.Ala552Thr Uncertain significance ★★ ⚠ same type
ITGA8 p.Ala848Ser Uncertain significance ★★ ⚠ same type
ITGA8 p.Arg588Gln Uncertain significance ★★ ⚠ same type
ITGA8 p.Asn40Thr Uncertain significance ★★ ⚠ same type
ITGA8 p.Glu815Asp 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/itga8-p-ser577phe (accessed [today's date]).

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