Is ELMOD3 p.Ile85Ser (c.254T>G) pathogenic?

ELMOD3 p.Ile85Ser (c.254T>G) is classified Likely benign in ELMOD3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.2132); Rare (popmax 0.157%, nfe).

How common is ELMOD3 p.Ile85Ser (c.254T>G) in the general population?

ELMOD3 p.Ile85Ser (c.254T>G) is rare (popmax 0.157%, nfe) (gnomAD).

What do computational predictors say about ELMOD3 p.Ile85Ser (c.254T>G)?

AlphaMissense predicts likely benign (score 0.2132) — an in-silico prediction, not a clinical call.

ELMOD3 p.Ile85Ser

c.254T>G · rs139481126 · VCV1582334

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2132 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2132	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -4.72	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 3.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 34 kb · p 0.0055 · regional, not allelic
Overall
CADD	24.1	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 0.157% European (non-Finnish) · 1,852/1,180,020 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.149%

Overall 0.128% 2,067/1,614,156 alleles · rare exomes 1,916/1,461,866 · genomes 151/152,290 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.157%	637
Admixed American	0.157%	638
Remaining individualsnot grpmax-eligible	0.107%	933
Finnishnot grpmax-eligible	0.0422%	2,371
African / African-American	0.0293%	3,411
South Asian	0.00439%	22,771
East Asian	0.00223%	44,884

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: ELMOD3
Protein: p.Ile85Ser
Coding: c.254T>G
MANE Select: NM_001135022
dbSNP: rs139481126
Type: single nucleotide variant
Location: chr2:85368740 (GRCh38)
Gene constraint: LOEUF 1.021 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.18

Full ELMOD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ELMOD3 p.Ala234Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala289Val Uncertain significance ★★ ⚠ same type
ELMOD3 p.Ala38Thr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Gln100Ter Uncertain significance ★★ same type
ELMOD3 p.Gln371Ter Uncertain significance ★★ same type
ELMOD3 p.His294Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.His297Tyr Uncertain significance ★★ ⚠ same type
ELMOD3 p.Leu164Met 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/elmod3-p-ile85ser (accessed [today's date]).

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